title: Muscle metabolism and activation heterogeneity by combined 31P chemical shift and T2 imaging, and pulmonary O2 uptake during incremental knee-extensor exercise.
abstract: The integration of skeletal muscle substrate depletion, metabolite accumulation, and fatigue during large muscle-mass exercise is not well understood. Measurement of intramuscular energy store degradation and metabolite accumulation is confounded by muscle heterogeneity. Therefore, to characterize regional metabolic distribution in the locomotor muscles, we combined 31P magnetic resonance spectroscopy, chemical shift imaging, and T2-weighted imaging with pulmonary oxygen uptake during bilateral knee-extension exercise to intolerance. Six men completed incremental tests for the following: (1) unlocalized 31P magnetic resonance spectroscopy; and (2) spatial determination of 31P metabolism and activation. The relationship of pulmonary oxygen uptake to whole quadriceps phosphocreatine concentration ([PCr]) was inversely linear, and three of four knee-extensor muscles showed activation as assessed by change in T2. The largest changes in [PCr], [inorganic phosphate] ([Pi]) and pH occurred in rectus femoris, but no voxel (72 cm3) showed complete PCr depletion at exercise cessation. The most metabolically active voxel reached 11 ± 9 mM [PCr] (resting, 29 ± 1 mM), 23 ± 11 mM [Pi] (resting, 7 ± 1 mM), and a pH of 6.64 ± 0.29 (resting, 7.08 ± 0.03). However, the distribution of 31P metabolites and pH varied widely between voxels, and the intervoxel coefficient of variation increased between rest (∼10%) and exercise intolerance (∼30-60%). Therefore, the limit of tolerance was attained with wide heterogeneity in substrate depletion and fatigue-related metabolite accumulation, with extreme metabolic perturbation isolated to only a small volume of active muscle (<5%). Regional intramuscular disturbances are thus likely an important requisite for exercise intolerance. How these signals integrate to limit muscle power production, while regional "recruitable muscle" energy stores are presumably still available, remains uncertain.
authors.affiliation: Rehabilitation Clinical Trials Center, Division of Respiratory & Critical Care Physiology & Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California;
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Cannon
authors.forename: Franklyn A
authors.initials: FA
authors.lastname: Howe
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Whipp
authors.forename: Susan A
authors.initials: SA
authors.lastname: Ward
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: McIntyre
authors.forename: Christophe
authors.initials: C
authors.lastname: Ladroue
authors.forename: John R
authors.initials: JR
authors.lastname: Griffiths
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Kemp
authors.forename: Harry B
authors.initials: HB
authors.lastname: Rossiter
mesh_terms: D000328:Adult; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000379:methods; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007717:Knee; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010100:Oxygen / Q000502:physiology*; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D052097:Quadriceps Muscle / Q000378:metabolism; D055815:Young Adult
chemical_list: D010725:Phosphocreatine; D010758:Phosphorus; D010100:Oxygen
keywords: exercise; magnetic resonance spectroscopy; oxygen uptake; quadriceps; skeletal muscle